Carcinogenesis Flashcards
What is a mutagen?
A compound that reacts with DNA and somehow changes the cell’s genetic makeup
What is an initiator?
A mutagen that predisposes cells to develop tumours
What are promoters?
Non-reactive compounds that stimulate tumour development
What is a complete carcinogen?
A compound which acts as both an initiator and a promoter, tumour development can occur without the application of another compound
What are the names of the steps of carcinogenesis?
Initiation Promotion Progression Hyperplasia Dysplasia Carcinoma in situ Cancer (Malignant tumours)
What happens during initiation?
Initiators react with DNA and can cause mutation Irreversible; the cell will be susceptible to promotion until its death
Any daughter cells produced from the mutated cell will also carry the mutation
What happens during promotion?
Promoters bind to receptor on mutated cell’s surface, in order to attract intracellular pathways that promote proliferation
What are the two general categories of promoter?
Specific = interact WITH RECEPTORS on or in target cells of defined tissue Non-specific = alter gene expression WITHOUT presence of a known RECEPTOR
What happens during progression?
Refers to the stepwise transformation of a benign tumour to a neoplasm and to malignancy
Associated with a karyotypic change since virtually all tumours that advance are aneuploid
What happens during hyperplasia?
The altered cell divides in an uncontrolled manner leading to an excess of cells in that region of tissue
Cells still have a normal appearance
What happens during dysplasia?
Additional genetic changes in hyperplastic cells lead to even more cell growth
Cells and tissue no longer look normal ‘disorganised structural architecture’
What happens during carcinoma in situ?
Cells and tissue look even more abnormal
Cells spread over a larger area, region of tissue involved primarily contains altered cell
Cells not metastised, therefore curable by surgery
Have potential to become invasive so treated as malignant
What happens during cancer (malignant tumours)?
These tumours have the ability to invade surrounding tissues and/or metastise
These metastatic tumours account for large percentage of cancer deaths
What tumour suppressor genes are mutated in colorectal cancer?
APC (at early stage of hyper-proliferation) and TP53 (in progression of late adenoma to carcinoma)
What oncogenes are mutated in colorectal cancer?
K-RAS (in progression of early to intermediate adenoma) and SRC
